Study of the combination of self-activating photodynamic therapy and chemotherapy for cancer treatment

Cancer is a very challenging disease to treat, both in terms of treatment eficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.This research was co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMPETE-POFC, grant number PTDC/QEQ-QFI/0289/2014; funded by FEDER through COMPETE2020, grant POCI-01-0145-FEDER-006980; funded by FEDER through NORTE2020, grant number NORTE-01-0145-FEDER 000028; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMEPETE2020-POCI, grant number POCI-01-0145-FEDER-007274; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER, grant number IF/00092/2014/CP1255/CT0004; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/140734/2018; funded by Fundação para a Ciência e Tecnologia (FCT), grant number UID/QUI/50006/2013; funded by Fundação para a Ciência e Tecnologia (FCT), grant number PTDC/BIA-MIA/29059/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number CEECIND/01425/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/143211/2019

Fungal infestation boosts fruit aroma and fruit removal by mammals and birds

For four decades, an influential hypothesis has posited that competition for food resources between microbes and vertebrates selects for microbes to alter these resources in ways that make them unpalatable to vertebrates. We chose an understudied cross kingdom interaction to experimentally evaluate the effect of fruit infection by fungi on both vertebrate (mammals and birds) fruit preferences and on ecologically relevant fruit traits (volatile compounds, toughness, etc). Our well-replicated field experiments revealed that, in contrast to previous studies, frugivorous mammals and birds consistently preferred infested over intact fruits. This was concordant with the higher level of attractive volatiles (esters, ethanol) in infested fruits. This investigation suggests that vertebrate frugivores, fleshyfruited plants, and microbes form a tripartite interaction in which each part could interact positively with the other two (e.g. both orange seeds and fungal spores are likely dispersed by mammals). Such a mutualistic view of these complex interactions is opposed to the generalized idea of competition between frugivorous vertebrates and microorganisms. Thus, this research provides a new perspective on the widely accepted plant evolutionary dilemma to make fruits attractive to mutualistic frugivores while unattractive to presumed antagonistic microbes that constrain seed dispersalinfo:eu-repo/semantics/publishedVersio

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Gastroenteric virus detection in fecal samples from women in Goiânia, State of Goiás, Brazil Detecção de vírus gastroentéricos em amostras fecais de mulheres em Goiânia, Estado de Goiás, Brasil

INTRODUCTION: This was a prospective study that included women seen in the obstetrics and gynecology sector of Hospital das Clínicas, Federal University of Goiás, in Goiânia, State of Goiás, with the aim of detecting rotaviruses, adenoviruses, caliciviruses and astroviruses. Eighty-four women participated in the study and from these, 314 fecal samples were collected. Out of all of the women, 29 were seropositive for HIV and 55 were seronegative, and 45 and 39 were pregnant and non-pregnant, respectively. METHODS: Fecal samples were collected from each woman once every two months over the period from July 2006 to June 2007, and they were screened for rotaviruses by means of polyacrylamide gel electrophoresis and immunoenzymatic assays, for caliciviruses and astroviruses by means of RT-PCR and for adenovirus by means of immunoenzymatic assays. The astroviruses were genotyped using nested PCR. RESULTS: Among the 84 patients, 19 (22.6%) were positive for either calicivirus (14/19) or astrovirus (6/19), while one women was positive for both viruses in fecal samples collected on different occasions. Most of the positive samples were collected during the months of July and August (astrovirus) and September and October (calicivirus). None of the samples analyzed was positive for rotavirus or adenovirus. Gastroenteric viruses were detected in 13/19 (68.4%) of the pregnant women, whether HIV-seropositive or not. CONCLUSIONS: The results from the present study showed that neither pregnancy nor HIV-seropositive status among the women increased the risk of infection by any of the gastroenteric viruses studied. This study presents data on gastroenteric virus detection among pregnant and/or HIV-positive women.<br>INTRODUÇÃO: Este foi um estudo prospectivo que incluiu mulheres atendidas no setor de obstetrícia e ginecologia do Hospital das Clínicas da Universidade Federal de Goiás, em Goiânia, Estado de Goiás com o objetivo de detectar rotavírus, adenovírus, calicivírus e astrovírus. Oitenta e quatro mulheres participaram no estudo e destas, 314 amostras fecais foram coletadas. Do total de mulheres, 29 eram soropositivas para HIV, 55 soronegativas, 45 e 39 estavam grávidas e não-grávidas, respectivamente. MÉTODOS: Amostras fecais foram coletadas de cada mulher uma vez a cada dois meses pelo período de Julho-2006 a Junho-2007, foram triadas para rotavírus pela metodologia de eletroforese em gel de poliacrilamida (EGPA) e através de ensaio imunoenzimático (EIE), para calicivírus e astrovírus por RT-PCR e por EIE para adenovírus. Os astrovírus foram genotipados por Nested-PCR. RESULTADOS: De 84 pacientes, 19 (22,6%) foram positivas para calicivírus (14/19) ou astrovírus (6/19), sendo que uma mulher foi positiva para ambos os vírus em amostras fecais coletadas em diferentes ocasiões. A maioria das amostras positivas foi coletada no período de Julho a Agosto (astrovírus) e de Setembro a Outubro (calicivírus). Nenhuma das amostras analisadas foi positiva para rotavírus ou adenovírus. Os vírus gastroentéricos foram detectados em 13/19 (68,4%) mulheres grávidas, as quais eram HIV-soropositivas ou não. CONCLUSÕES: Os resultados do presente estudo mostram que nem o estado gravídico das mulheres nem a soropositividade para HIV aumentaram o risco para a infecção por nenhum dos vírus gastroentéricos estudados. Este estudo apresenta dados sobre a detecção de vírus gastroentéricos entre mulheres grávidas e/ou HIV-positivas